ArticleMolecular and cellular biology2007
Ligand binding to the androgen receptor induces conformational changes that regulate phosphatase interactions.
Article in Molecular and cellular biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 56 citations in OpenAlex.
- Sex-specific regulation of the cardiac transcriptome by the protein phosphatase 2A regulatory subunit B55α.npj metabolic health and disease · 2024Article
- Review
- Induction of PARP7 Creates a Vulnerability for Growth Inhibition by RBN2397 in Prostate Cancer Cells.Cancer research communications · 2023Article
- Review
- Androgen signaling uses a writer and a reader of ADP-ribosylation to regulate protein complex assembly.Nature communications · 2021Article
- Posttranslational regulation of androgen dependent and independent androgen receptor activities in prostate cancer.Asian journal of urology · 2020Review
- Small-Molecule Activators of Protein Phosphatase 2A for the Treatment of Castration-Resistant Prostate Cancer.Cancer research · 2018Article
- Differential regulation of the androgen receptor by protein phosphatase regulatory subunits.Oncotarget · 2018Article
- Positive feedback loop mediated by protein phosphatase 1α mobilization of P-TEFb and basal CDK1 drives androgen receptor in prostate cancer.Nucleic acids research · 2017Article
- Article
- Preventing the Androgen Receptor N/C Interaction Delays Disease Onset in a Mouse Model of SBMA.Cell reports · 2015Article
- Androgen receptor phosphorylation: biological context and functional consequences.Endocrine-related cancer · 2014Review
- Androgen induces a switch from cytoplasmic retention to nuclear import of the androgen receptor.Molecular and cellular biology · 2013Article
- Posttranslational modification of the androgen receptor in prostate cancer.International journal of molecular sciences · 2013Review
- A regulatory feedback loop between Ca2+/calmodulin-dependent protein kinase kinase 2 (CaMKK2) and the androgen receptor in prostate cancer progression.The Journal of biological chemistry · 2012Article
- Identification of androgen receptor phosphorylation in the primate ovary in vivo.Reproduction (Cambridge, England) · 2010Article
- FKBP51 promotes assembly of the Hsp90 chaperone complex and regulates androgen receptor signaling in prostate cancer cells.Molecular and cellular biology · 2010Article
- Immunohistochemical validation of multiple phospho-specific epitopes for estrogen receptor alpha (ERalpha) in tissue microarrays of ERalpha positive human breast carcinomas.Breast cancer research and treatment · 2009Article
- Androgen receptor phosphorylation and activity are regulated by an association with protein phosphatase 1.The Journal of biological chemistry · 2009Article
- Nuclear actin and actin-binding proteins in the regulation of transcription and gene expression.The FEBS journal · 2009Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We describe a mechanism for protein phosphatase 2A (PP2A) targeting to the androgen receptor (AR) and provide insight into the more general issue of kinase and phosphatase interactions with AR. Simian virus 40 (SV40) small t antigen (ST) binding to N-terminal HEAT repeats in the PP2A A subunit induces structural changes transduced to C-terminal HEAT repeats. This enables the C-terminal HEAT repeats in the PP2A A subunit, including HEAT repeat 13, to discriminate between androgen- and androgen antagonist-induced AR conformations. The PP2A-AR interaction was used to show that an AR mutant in prostate cancer cells (T877A) is activated by multiple ligands without acquiring the same conformation as that induced by androgen. The correlation between androgen binding to AR and increased phosphorylation of the activation function 1 (AF-1) region implies that changes in AR conformation or chaperone composition are causal to kinase access to phosphorylation sites. However, AF-1 phosphorylation sites are kinase accessible prior to androgen binding. This suggests that androgens can enhance the phosphorylation state of AR either by negatively regulating the ability of the ligand-binding domain to bind phosphatases or by inducing an AR conformation that is resistant to phosphatase action. SV40 ST subverts this mechanism by promoting the direct transfer of PP2A onto androgen-bound AR, resulting in multisite dephosphorylation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.